How Does DNA Work?
DNA is an information storage molecule that lives inside almost every cell in the body. If we think of our genome as the recipe book, then chromosomes are chapters, and genes are recipes.
What can we make with these genetic recipes? Only the most delicious, life-sustaining proteins, such as hormones, antibodies, and enzymes.
Taking the form of a double helix, DNA is made up of two strands of complementary base pairs known as adenine, cytosine, guanine, and thymine.
Human DNA contains 3 billion base pairs. However, only a tiny fraction of these are protein-coding genes. In humans, genes range in length from a few hundred to more than 2 million bases.
The structure of DNA was intuited 70 years ago, based on just a handful of clues being applied to the rules of chemical bonding.
It's the precise sequence of A, T, C, and G bases within genes that creates the diversity of life. In The Mysterious World of The Human Genome, Frank Ryan offers the analogy of a train track that stretches to the horizon, with three billion sleepers representing base pairs.
Base pairing of DNA is extremely reliable. But mistakes do occur—at an estimated rate of 1 in 100 million bases per generation in humans. This is how we get mutations which alter our genetic code.
How Does DNA Work?
Now that we have an idea of the structure, how does DNA work? How does it keep us alive on a moment-to-moment basis?
Let's zoom out to our cells: the multipurpose biological factories that make up our tissues. Cells have complex internal structures bustling with organelles and proteins that keep us alive.
Besides water and fat, our bodies are made almost entirely of proteins. They include enzymes that drive digestion, hormones that coordinate growth, and antibodies that neutralise invading pathogens.
DNA isn't only a blueprint for foetal growth. It's essential to our ongoing survival, such as making insulin if we've just had breakfast, or cortisol to regulate our stress response.
To make new proteins, specific genes from our master DNA must first be copied into single-stranded molecules of messenger RNA (mRNA). They exit the nucleus and make their way to the factory floor, better known as the cytoplasm.
It's here that mRNA is translated into long chains of amino acids called peptides. These complex molecules twist and fold into specific functional proteins. The correct DNA blueprint must be followed accurately for proteins to do their jobs around the body.
How exactly is DNA used to make proteins? I hope you're sitting down, because here comes an exquisite bit of molecular biology.
How DNA Expression Works
The Central Dogma describes the one-way flow of genetic information from DNA to proteins. We're going to examine three major stages here: transcription, processing, and translation.
Step 1. Transcription
So you've got a bunch of DNA hanging around in the nucleus. It's time to express some genes.
A dedicated protein known as RNA polymerase attaches itself to the DNA. It teases apart the two strands of the double helix, unwinding the ladder as it travels along the length of a gene.
This exposes the DNA anti-sense strand, which contains complementary bases according to the DNA sense strand.
The RNA polymerase multitasks. As it unwinds the DNA, it reads the individual bases, and builds a new molecule based on complementary pairing.
The ingredients are free-floating nucleotides: A, T, C, and G bases with a sugar-phosphate backbone attached. The emerging genetic string is called pre-messenger RNA.
It's a beautiful molecular dance. And it's happening at astonishing speed in your cells right now, all driven by spontaneous chemical interactions.
Step 2. RNA Processing
The DNA recipe book is written in such a way that a single recipe can be cut-and-paste to produce multiple alternative dishes. The biological term for this is alternative splicing.
So let's customise the dish. Still inside the nucleus, spliceosomes approach the pre-mRNA sequence to make their edits.
Spliceosomes cut out non-coding sequences of bases called introns and leave behind select coding sequences called exons.
On average, there are 9 exons per gene, although the supremely long dystrophin gene has 79 exons spanning 2.3 million bases. That's some heavy gene editing right there.
Step 3. Translation
So far, we've just been tinkering with the gene recipe. Now we need a chef to actually source the ingredients and produce the dish.
The finished messenger RNA strand exits the nucleus and lands in the fluid cell cytoplasm. This is the kitchen floor. Here, a ribosome binds to the start of the mRNA and does something remarkable.
Ribosomes read the mRNA in groups of three bases called codons. These are matched to complementary anticodons.
Free-floating transfer RNA units approach the ribosome, each carrying an amino acid matched to a specific anticodon. Spontaneous chemical bonding sees the mRNA translated into the desired sequence of amino acids.
How Amino Acids Create Proteins
Amino acid chains—or peptides—begin with a primary structure: a linear string of amino acids connected by covalent bonds. But this doesn't last long.
During translation, amino acids form weak hydrogen bonds between one other, twisting and folding the chain into alpha helices and beta sheets. These are secondary structures.
Tertiary structures are more complex yet. As amino acids fold and meet, they spontaneously form ionic bonds, disulphide bridges, and hydrophilic and hydrophobic interactions. This secures them into 3D proteins with unique forms. And when multiple polypeptide chains convene, they produce the largest of all proteins with complex quaternary structures.
At this point, the new proteins are packaged off to their destination outside the cell, or retained within as new cell workers.
The Genetic Code
"Tell me more about the codons!" I hear you scream. And you'd be right. This is a good thing to scream about, if anything is.
The RNA alphabet has only four letters (A, U, C, G). Since codons occur in groups of three, it means there are only 64 words in our codon dictionary.
Yet because human cells can only produce 20 different amino acids, it leaves us with a fair bit of redundancy in the genetic code. In other words, each amino acid tends to be associated with more than one codon.
Genes begin with a start codon, the most common of which is AUG, which also translates to the amino acid methionine. So this amino acid is usually docked first at the ribosome.
Likewise, genes finish up with a stop codon; either UAG, UGA, or UAA. These don't translate to any amino acids and just signal the end of the peptide chain.
Amino Acid Key
|Ala = Alanine||Leu = Leucine|
|Arg = Arginine||Lys = Lysine|
|Asn = Asparagine||Met = Methionine|
|Asp = Aspartic Acid||Phe = Phenylalanine|
|Cys = Cysteine||Pro = Proline|
|Gln = Glutamine||Ser = Serine|
|Glu = Glutamic Acid||Thr = Threonine|
|Gly = Glycine||Trp = Tryptophane|
|His = Histidine||Tyr = Tyrosine|
|Ile = Isoleucine||Val = Valine|
How Fast Does DNA Work?
Depending on the size of the gene, it takes between 20 seconds and several minutes to produce a typical protein molecule from mRNA.
Multiple ribosomes can work along the same mRNA strand, just 80 nucleotides apart, to produce multiple proteins simultaneously. And there are up to 10 million ribosomes in each cell, all building proteins on-demand alongside other cells.
It's all rather amazing really. DNA and its entourage perform a constant choreography, culminating in the normal functioning of any living organism, such as a friendly old toad. Isn't that brilliant?